Kalytera Therapeutics, Inc. (TSXV:KALY) (“Kalytera”) today announced preliminary results of a 12 patient Phase 2a study evaluating the safety and efficacy of prolonged use of cannabidiol (“CBD”) in the prevention of Graft versus Host Disease (“GvHD”). Preliminary results of the study demonstrate that only 15% of patients in the CBD treatment group developed Grade 2-4 GvHD, as compared to a 60-70% incidence predicted by historical data used as a control. The study was conducted by Talent Biotechs Ltd. (“Talent”), a privately held, Israeli-based developer of CBD therapeutics.
Kalytera previously announced that it has entered into a binding letter of intent (the “LOI”) to acquire Talent and its Phase 2 program in GvHD (the “Transaction”).
GvHD is an orphan disease that can arise following allogeneic hematopoietic cell transplantation (“HCT”). GvHD occurs when the transplanted donor cells attack the patient’s organs, including the skin, gastrointestinal tract, liver, lungs, eyes, oral cavity, heart, nervous system and other organs. GvHD is associated with acute and chronic illness, infections, disability, reduced quality of life, and death. The ability to prevent GvHD is a major unmet need. Despite prophylactic immunosuppressive treatment, GvHD remains a major cause of mortality following HCT.
In 2015, Dr. Moshe Yeshurun, Chief Medical Officer of Talent, published the results of a prior Phase 2a clinical trial evaluating the safety and efficacy of CBD in the prevention of acute GvHD1. Based on the promising results of that study, Talent commenced the present Phase 2a clinical study to evaluate the efficacy of prolonged administration of CBD following HCT. In this study, which enrolled 12 patients, participants were provided daily doses of CBD seven days prior to transplantation and for 100 days following the procedure. With a median follow up of 8.5 months following transplantation, results demonstrate that 85% of the patients did not develop significant (Grades 2-4) acute GvHD, despite the fact that the majority of the patients (10) received stem cells from unrelated donors, including five patients who received stem cells from non-fully matched donors. Only 15% of patients developed grade 2-4 GvHD, versus the predicted incidence of 60-70% in the scientific literature, potentially representing a more than four-fold reduction.
“The results of these clinical studies are outstanding, and mark a major milestone in the potential prevention of this serious and disabling disorder following HCT,” said Dr. Andrew Salzman, CEO of Kalytera.
Talent also completed additional pilot studies exploring the use of CBD in treatment of GvHD, including treatment of acute and chronic GvHD. Following the anticipated completion of the Talent acquisition, Kalytera will initiate planning for placebo-controlled, double blind, randomized studies of CBD for both the prevention and treatment of GvHD. These clinical studies may support U.S. Food and Drug Administration (“FDA”) Breakthrough Therapy and Fast Track Designations, which could accelerate the regulatory approval process.
About Graft versus Host Disease
A hematopoietic stem cell transplantation (“HCT”) is a procedure where the stem cells of the bone marrow or peripheral blood of a healthy donor are transplanted into a new host after chemotherapy or radiation. This is a lifesaving procedure for many diseases of the blood and bone marrow including leukemia, Hodgkin and Non-Hodgkin lymphoma, multiple myeloma, sickle cell anemia, and thalassemia. There were over 8,000 HCT procedures in the U.S. in 20142 and the use of HCT procedures is expected to continue to increase. While HCT procedures can be lifesaving, they pose many dangerous side effects, including infection and GvHD.
GvHD is a multisystem disorder that occurs when the transplanted cells from a donor (“the graft”) recognize the transplant recipient (“the host”) as foreign. This interaction initiates an immune reaction that causes disease in the transplant recipient. This reaction can occur within days after the transplant (acute GvHD) or months to years after HCT (chronic GvHD).
GvHD can be mild, moderate, severe, and even life threatening. Patients with acute GvHD may suffer from rashes and blistering of the skin, nausea, vomiting, abdominal cramps accompanied by diarrhea, and jaundice. Generally, acute reactions are more severe and life threatening.
GvHD is a major cause of morbidity and mortality following HCT. Researchers estimate that even with intensive prophylaxis with immunosuppressive treatments, 30-50% of patients transplanted from fully matched sibling donors and 50-70% of patients transplanted from unrelated donors will develop some level of GvHD3. The GvHD market was valued at $295M across the six major markets in 2013, and is expected to grow to $544M by 2023, according to the research and consulting firm GlobalData4.
Standard of Care: Prevention and Treatment of GvHD
The first step in prevention of GvHD is the selection of donor cells that closely match the genetics of the immune system of the transplant recipient, ideally a sibling donor. From there, the patient relies on drugs that have been developed to prevent or treat GvHD. Medicinal prevention of acute GvHD is dependent on immunosuppression of the donor cells, either pharmacologically or through T cell depletion. Common drugs include methotrexate, cyclosporine tacrolimus, sirolimus, mycophenolate mofetil and ATG. Preventive measures and clinical practices vary by institution5.
Treatment of GvHD involves pharmacologic suppression of the graft’s immune cell activation and reestablishment of donor-host immune-tolerance. Most patients are prescribed corticosteroids, which directly suppress the donor’s immune cell attack on host tissue, but also raise the risk of infection and cancer relapse. As with prevention, the optimal drug strategy for GvHD is not well defined. Only 30-50% of patients with moderate to severe GvHD respond to corticosteroids, putting many at risk for fatal outcomes6. Better treatment options are needed to improve the mortality and morbidity outcomes for transplant recipients.
CBD and GvHD
CBD is a major component of cannabis sativa, commonly known as marijuana. CBD possesses potent anti-inflammatory and immunosuppressive properties. Unlike the other major component of cannabis, tetrahydrocannabinol (“THC”), CBD is non-psychoactive and is well tolerated by humans when taken over extended periods of time7. CBD has shown benefit in a number of models of inflammatory diseases including diabetes8, rheumatoid arthritis9, multiple sclerosis10, and inflammatory bowel disease11.
- Yeshurun M, Shpilberg O, Herscovici C, et al. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study. Biol Blood Marrow Transplant. 2015;21(10):1770-5.
- Center for International Blood and Marrow Transplant Research (CIBMTR) HCT Trends and Survival Data
- Weisdorf D. GVHD the nuts and bolts. Hematology Am Soc Hematol Educ Program. 2007;:62-7.
- GlobalData Report (2015)
- Ruutu T, Van biezen A, Hertenstein B, et al. Prophylaxis and treatment of GVHD after allogeneic haematopoietic SCT: a survey of centre strategies by the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012;47(11):1459-64.
- Weisdorf D. GVHD the nuts and bolts. Hematology Am Soc Hematol Educ Program. 2007;:62-7.
- Mechoulam R, Peters M, Murillo-rodriguez E, Hanus LO. Cannabidiol–recent advances. Chem Biodivers. 2007;4(8):1678-92.
- Weiss L, Zeira M, Reich S, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39(2):143-51.
- Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA. 2000;97(17):9561-6.
- Trojano M. Advances in the management of MS symptoms: real-life evidence. Neurodegener Dis Manag. 2015;5(6 Suppl):19-21.
- Schicho R, Storr M. Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice. Pharmacology. 2012;89(3-4):149-55.
Kalytera (TSXV:KALY) is pioneering the development of a next generation of cannabinoid therapeutics. Through its proven leadership, drug development expertise, and intellectual property portfolio, Kalytera seeks to establish a leading position in the development of novel cannabinoid medicines for a range of important unmet medical needs.
Kalytera is focused first on developing a new class of proprietary cannabidiol (“CBD”) therapeutics. CBD is a remarkable compound that has shown activity against a number of pharmacological targets. However, there are limitations associated with natural CBD, including its poor oral bioavailability and short half-life. Kalytera is developing innovative CBD formulations and prodrugs in an effort to overcome these limitations, and to target specific disease sites within the body. Kalytera intends to file composition of matter and method of use patents covering its novel inventions, with the goal of limiting future competition.
Completion of the proposed Transaction is subject to a number of conditions including, but not limited to, completion of satisfactory due diligence, execution of the definitive agreement in respect of the proposed Transaction, TSXV acceptance and, if applicable, shareholder approval. Where applicable, the proposed Transaction cannot close until the required shareholder approval is obtained. There can be no assurance that the proposed Transaction will be completed as proposed, or at all.
Investors are cautioned that any information released or received with respect to the proposed Transaction may not be accurate or complete and should not be relied upon. Trading in the securities of Kalytera should be considered highly speculative.
Neither the TSXV nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) has in any way passed upon the merits of the proposed Transaction and associated transactions and neither of the foregoing entities has in any way approved or disapproved of the contents of this press release.
Neither the TSXV nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) accepts responsibility for the adequacy or accuracy of this press release.
This news release contains “forward-looking information” within the meaning of applicable securities laws relating to the proposed Transaction including statements regarding the terms and conditions of the proposed Transaction, as well as information relating to Talent. The information about Talent contained in the press release has not been independently verified by Kalytera. Although Kalytera believes in light of the experience of its officers and directors, current conditions and expected future developments and other factors that have been considered appropriate, that the expectations reflected in this forward-looking information are reasonable, undue reliance should not be placed on them because Kalytera can give no assurance that they will prove to be correct. Readers are cautioned to not place undue reliance on forward-looking information. Actual results and developments may differ materially from those contemplated by these statements depending on, among other things, the risks that the parties will not proceed with the proposed Transaction; that the ultimate terms of the proposed Transaction will differ from those that currently are contemplated by the LOI; and that the proposed Transaction will not be successfully completed for any reason (including the failure to obtain the required approvals or clearances from regulatory authorities). The terms and conditions of the proposed Transaction may change based on Kalytera’s due diligence and the receipt of tax, corporate and securities law advice for both Kalytera and Talent. The statements in this press release are made as of the date of this release. Kalytera undertakes no obligation to comment on analyses, expectations or statements made by third-parties in respect of Kalytera, Talent, their securities, or their respective financial or operating results (as applicable). Kalytera disclaims any intent or obligation to update publicly any forward-looking information, whether as a result of new information, future events or results or otherwise, other than as required by applicable securities laws.